QTc prolongation is a common and well-documented side-effect of ATO, while it is not observed with ATRA treatment. QT prolongation can lead to torsade de pointes-type ventricular arrhythmia, which can be potentially fatal. The GIMEMA-SAL-AMLSG APL0406 trial reported prolonged QTc interval in 15 patients in the ATRA–ATO group (16%) [
20
]. Clinically significant arrhythmias are very rare and none has been reported in the most recent trials employing ATO as first-line therapy. Patients with a prolonged QTc interval above 500 ms, according to international guidelines, are recommended to maintain potassium and magnesium concentrations above 4.0 mEq/l and 1.8 mg/dl, ATO should be withheld, electrolytes repleted and other drugs that may cause prolonged QTc interval potentially discontinued until normalization of the QTc [
29
]. A recent analysis from US investigators assessed QT intervals in 113 non-APL patients treated with ATO using four different correction formulas of the QT interval [
63
]. With a commonly used Bazett rate correction formula, 90% of patients had QTc greater than 470 ms, including 65% above 500 ms. Using other rate correction formulas (i.e. Framingham and Fredericia), only 24%–32% of patients had rate-corrected QT intervals above 500 ms. It is, therefore, conceivable that 500 ms QTc calculated with formulas other than Bazett should be an acceptable threshold to withhold ATO treatment [
63
]. Hepatic toxicity has frequently been reported in studies employing ATO with or without ATRA, especially in terms of increase in liver enzymes (mostly AST and ALT and less frequently alkaline phosphatase and bilirubin). This complication may occur in up to 60% of cases [
20
]; however, it is generally reversible and successfully managed with a decrement or temporary discontinuation of ATO and/or ATRA. No cases of hepatic failure have been reported in recent trials [
20
,
21
].

The development of hyperleukocytosis is a well-known and frequent side-effect occurring in APL patients receiving ATO and/or ATRA. In the APL0406 study including low- and intermediate-risk patients, leukocytosis defined as WBC >10 × 10
9
/l was reported in 47% of patients in the ATRA–ATO combination group and was managed using hydroxyurea as per protocol recommendation [
20
]. In the NCRI Study AML17, patients with a peripheral WBC count of >10 × 10
9
/l at baseline (high risk) had a provision to receive GO 3 mg/m
2
on day 1 of treatment and on day 4 if the white count had not fallen below 10 × 10
9
/l. In addition, a fraction of low-risk patients developing hyperleukocytosis received a single dose of GO upon rise of WBC count of 10 × 10
9
/l [
21
].

Early death before treatment or during the initial days of therapy remains the main obstacle to the final cure of APL. Efforts in this area should focus both on education to improve prompt diagnosis and early management and on clinical and laboratory research to identify predictive factors of severe hemorrhage. The use of ATO, the most active single agent in this disease, should be expanded to other patient subsets where there is still very limited experience including high-risk disease, children and the elderly population. Finally, it is likely that oral arsenic derivatives that have been shown to be equally effective will in the near future substitute the i.v. formulation, in combination with ATRA, thus allowing an entirely oral management of the disease.

Thank you for the information Tracy. You were right about the MTHFR mutation. I am compound heterozygous for the two variants. As I understand it, MTHFR mutation can cause neuropathy in and of itself and the gene requires adequate B12 to function as well. With my B12 deficiency and MTHFR mutation, no wonder I have neuropathy.

Your daughter should also be taking B12. You both should also be taking D3 and Magnesium.

Have you been checked for Celiac? I believe that runs in families. Try to eat as organic as you can, and if you have the room, grow your own veggies. The more I read and hear, the more squeamish I am about our food supply. It doesn’t stop me from eating Taco Bell and then Peanut Chews, you understand, but at least I know that stuff is not supposed to be good for me.

Does anyone else have trouble posting here? Overtime I go to post something, I get an error message that the site’s server is down, so I click the button that says to try a live version, then I hit the back button, and there is my post. Today, when I add a post, and then try to add another, my first post is still in the comments section. Is it me, or the site? Either way, it’s frustrating, especially the times when my post does not appear.

Ann, yes that happens to me when I post to this page, I just ignore the error. I think it might be due to so many comments attached to this particular page. This has got to be one of the most highly commented on pages Chris Kesser has on his blog.